Surgery for Central Nervous System Tuberculosis in Children.

Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Central nervous system tuberculosis is widely prevalent in the world, especially in the developing countries and continues to be a socioeconomic problem. It is highly devastating form of tuberculosis leading to unacceptable levels of morbidity and mortality despite appropriate antitubercular therapy. The clinical symptoms are varied and nonspecific. They can be easily overlooked. Tuberculous meningitis is the most common presentation and its sequelae viz. vasculitis, infarction and hydrocephalus can be devastating. The ensuing cognitive, intellectual, and endocrinological outcome can be a significant source of morbidity and mortality, especially in resource constrained countries. Early diagnosis and treatment of tuberculous meningitis and institution of treatment is helpful in limiting the course of disease process. The diagnosis of CNS tuberculosis remains a formidable diagnostic challenge. The microbiological methods alone cannot be relied upon. CSF diversion procedures need to be performed at the appropriate time in order to achieve good outcomes. Tuberculous pachymeningitis and arachnoiditis are morbid sequelae of tuberculous meningitis. Tuberculomas present as mass lesions in the craniospinal axis. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Tuberculosis of the spinal cord is seen similar to intracranial tuberculosis in pathogenesis but with its own unique clinical manifestations and management. Multidrug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted. The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized. Heightened clinical suspicion is paramount to ensure prompt investigation. Early diagnosis and treatment are essential to a gratifying outcome and prevent complications.

Effectiveness of Adjunctive High-Dose Infliximab Therapy to Improve Disability-Free Survival Among Patients With Severe Central Nervous System Tuberculosis: A Matched Retrospective Cohort Study.

BACKGROUND: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. METHODS: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. RESULTS: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. CONCLUSIONS: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.

Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study.

BACKGROUND: Central nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient's immune status alters the clinical manifestations and treatment outcomes of CNS TB. METHODS: Between January 2007-December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID). RESULTS: Of 310 subjects, 160 (51.6%) were in the ID group-132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status -HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups. CONCLUSIONS: TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.

Tuberculosis revisted: classic imaging findings in childhood.

Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.

Neuroimaging of central nervous system tuberculosis.

A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.

Time Elapsed from onset of symptoms to antituberculosis treatment in children with central nervous system tuberculosis in a tertiary hospital in South India: A mixed-methods pilot study.

A pilot study with a mixed-methods design was conducted to estimate the time for tuberculosis (TB) treatment initiation and associated factors among children with central nervous system-TB (CNS-TB). A total of 38 children were enrolled for the quantitative component, and 20 in-depth interviews were conducted. The median duration (interquartile range) from onset of symptoms to treatment initiation was 23 (11, 55) days. About 44% and 31% of the children presented with Stage II and Stage III of CNS-TB, respectively. The major reasons for delay were symptoms not taken seriously (50%) and too many referrals (21%). About 89% of the families went into catastrophic health expenditure due to the disease. The treatment delay may be due to both patient delay and health system delay. Tailoring approaches to target the pediatric population could further improve early detection and treatment initiation of CNS-TB.

Nos2-/- mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis.

BACKGROUND: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. METHODS: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. RESULTS: Intra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. CONCLUSIONS: Intra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

Pelvic and central nervous system tuberculosis complicated by a paradoxical response manifesting as a spinal tuberculoma: a case report.

BACKGROUND: The post-partum period is a risk factor for tuberculosis (TB), possibly including the period after miscarriage as illustrated here. This case demonstrates how non-specific symptoms can hide widely disseminated TB. CASE PRESENTATION: A healthy 26-year-old female with a history of recent miscarriage presented to the emergency department with non-specific symptoms of headache, abdominal pain, and sub-acute fevers. She had immigrated to the United States from the Marshall Islands 9 years prior. Two months prior to presentation she had a miscarriage at 18 weeks of pregnancy. On admission, transvaginal ultrasound revealed retained products of conception and abdominal computed tomography revealed findings consistent with tubo-ovarian abscesses and peritonitis. The obstetrics and gynecology service performed dilation and curettage (D&C) to remove retained products of conception. Acid-fast bacilli cultures from cerebrospinal fluid as well as specimens from D&C and intra-abdominal abscesses subsequently all grew TB. She was diagnosed with TB meningitis, peritonitis, endometritis, and tubo-ovarian abscesses. Her treatment course was complicated by a paradoxical response resulting in a spinal tuberculoma causing lower extremity weakness. The tuberculoma was treated with surgical decompression as well as continuation of treatment with anti-tubercular chemotherapy and steroids. CONCLUSION: Disseminated and extrapulmonary TB can present with non-specific symptoms. Recognition of risk factors for TB is critical for prompt diagnostic evaluation and treatment of this deadly disease. A paradoxical reaction needs to be taken into consideration when any new neurological symptoms occur during TB treatment.

Thalidomide Use for Complicated Central Nervous System Tuberculosis in Children: Insights From an Observational Cohort.

BACKGROUND: Much of the neurological sequelae of central nervous system (CNS) tuberculosis (TB) is due to an excessive cytokine-driven host-inflammatory response. Adjunctive corticosteroids, which reduce cytokine production and thus dampen the inflammation, improve overall survival but do not prevent morbidity. This has prompted investigation of more targeted immunomodulatory agents, including thalidomide. METHODS: We describe a retrospective cohort of 38 children consecutively treated with adjunctive thalidomide for CNS TB-related complications over a 10-year period. RESULTS: The most common presenting symptom was focal motor deficit (n = 16), followed by cranial nerve palsies and cerebellar dysfunction. Three of the 38 children presented with large dural-based lesions, manifesting as epilepsia partialis continua (EPC), 4 presented with blindness secondary to optochiasmatic arachnoiditis, and 2 children developed paraplegia due to spinal cord TB mass lesions. Duration of adjunctive thalidomide therapy (3-5 mg/kg/day) varied according to complication type. In children compromised by TB mass lesions, the median treatment duration was 3.9 months (interquartile range [IQR], 2.0-5.0 months), whereas in children with optic neuritis it was 2.0 months (IQR, 1.3-7.3 months) and in EPC it was 1.0 months (IQR, 1-2.5 months). Satisfactory clinical and radiological response was observed in 37 of the children. None of the children experienced rashes, hepatitis, or hematologic derangements or complained of leg cramps. CONCLUSIONS: This study is the largest cohort of adult or pediatric patients treated with adjunctive thalidomide for CNS TB-related complications. The drug has proved to be safe and well tolerated and appears to be clinically efficacious. The potential role of thalidomide or analogues in the treatment of other tuberculous meningitis-related complications requires further exploration.

Central nervous system tuberculosis.

PURPOSE OF REVIEW: Central nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis. RECENT FINDINGS: Insight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival. SUMMARY: Recent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.

A woman with disseminated tuberculosis experienced preterm delivery, fallopian tube pregnancy, and delivered successfully following in vitro fertilization: a case report.

BACKGROUND: Disseminated tuberculosis (TB) is a fatal disease resulting from hematogenous dissemination of Mycobacterium tuberculosis. Spontaneous pregnancy rate of women with TB is low; furthermore, live birth, spontaneous abortion or ectopic pregnancy may be the outcomes even if pregnancy occurs. CASE PRESENTATION: We report a case of a woman with disseminated TB who had a series of complications including preterm delivery with congenital TB and infant death of pulmonary TB, fallopian tube pregnancy. She was treated by in vitro fertilization-embryo transfer (IVF-ET), and gave birth to a healthy baby. CONCLUSION: Disseminated TB has a significant impact on female fertility. We should take more active efforts to diagnose and treat this disease in a timely fashion. Moreover, IVF treatment is a feasible approach for an infertile woman after TB.

Giant central nervous system tuberculoma in pediatric patients: surgical case series.

Central nervous system tuberculoma is rare and challenging situation. Clinical records of patients with pathologically proven tuberculoma were retrospectively reviewed. Clinical presentation, lesion location, radiological characteristics, perioperative and surgical management, and outcome is summarized and analyzed. Eight patients were included and there was one girl. Age ranged from 3 to 14 years with mean age 9.8 years. Clinical duration ranged from 20 days to 2 years, and 3 patients had previous lung tuberculosis with anti-TB treatment. The lesion was in cerebellum in 6 cases, including 1 involving basal ganglia and 1 involving thalamus. The lesion was in basal ganglia, thalamus, and third ventricle in 1 case, and in T12-L1 spinal cord in another. Cerebellar lesion was resected via paramedian suboccipital approach in 5 patients, basal ganglia lesion via trans-cortical frontal horn approach in 2 patients, and intra-spinal lesion via trans-laminar approach in 1 patient. Follow-up ranged from 10 to 24 months. Of the 8 patients, 6 returned to normal life. One patient had cerebellar lesion resected and the thalamic lesion reduced in size after anti-TB treatment. One patient died from TB spreading. Our data showed that most patients can be successfully treated by resection of the lesion. Low T2 signal, ring shaped enhancement and peripheral edema strongly suggest tuberculoma. Empirical anti-TB treatment should be initiated perioperatively.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Drug Resistance in Children with Central Nervous System Tuberculosis from a Tertiary Care Center in Mumbai.

INTRODUCTION: Central Nervous System tuberculosis (CNS-TB) is the most lethal form of extra-pulmonary TB, especially in children. In this study, we have discussed patterns of drug resistance in pediatric CNS-TB. MATERIALS AND METHODS: Prospective observational study conducted on 100 children at a tertiary care center. Diagnosed cases of CNS-TB were enrolled. GeneXpert MTB/RIF was used upfront for diagnosis, and in cases where TB MGIT culture was positive, a phenotypic Drug Susceptibility Test (DST) was done. Patients were divided into resistant to at least one drug (DR) and drug-susceptible (DS). Various parameters were compared between these groups. RESULTS: Mean age of participants was 5.84 ± 3.5 years, with a male-to-female ratio of 1.08 : 1; 14% of children had drug-resistant CNS TB (DR-CNS-TB). A higher proportion of children previously treated for TB were associated with drug resistance (p = 0.009), and those with disseminated TB also had a higher drug resistance (p = 0.002). Apart from this, the DR and DS groups had no statistically significant differences in demographic, clinical or epidemiological parameters. CONCLUSIONS: Previous history of being treated for TB and disseminated TB was an independent risk factor for DR-CNS-TB. Ensuring proper adherence and compliance to anti-tubercular treatment could help in preventing the emergence of DR TB.

Cognitive impairment in patients with central nervous system tuberculosis.

INTRODUCTION: Tuberculosis (TB) in Mexico remains an important cause of morbidity and mortality; in the past 4 years, 110,681 cases of pulmonary tuberculosis and 1571 cases of tuberculous meningitis were reported. OBJECTIVE: To determine the neurocognitive sequelae, clinical presentation and neuroimaging alterations in patients with central nervous system tuberculosis. METHODS: A retrospective, analytical, and cross-sectional study was carried out from 2010 to 2019. Patients with central nervous system tuberculosis, with and without HIV/AIDS coinfection, were included. RESULTS: During the study period, 104 cases with a definitive or probable central nervous system tuberculosis diagnosis were included; 38% had HIV/AIDS coinfection, and 55%, various comorbidities (p = 0.0001); 49% had cognitive alterations, and 14% died. CONCLUSIONS: Although HIV/AIDS infection can contribute to cognitive decline in patients with tuberculous meningitis, no differences were observed between patients with and without HIV/AIDS. Cognitive sequelae showed improvement during follow-up with adequate management and therapeutic control of the patients.

INTRODUCCIÓN: La tuberculosis en México sigue siendo causa importante de morbimortalidad; en los últimos cuatro años, se reportaron 110 681 casos de tuberculosis pulmonar y 1571 casos de tuberculosis meníngea. OBJETIVO: Determinar las secuelas neurocognoscitivas, presentación clínica y alteraciones en los estudios de neuroimagen en pacientes con tuberculosis del sistema nervioso central. MÉTODOS: Se realizó un estudio retrospectivo, analítico y transversal de 2010 a 2019. Se incluyeron pacientes con tuberculosis del sistema nervioso central, con y sin coinfección por VIH/sida. RESULTADOS: Durante el periodo de estudio se incluyeron 104 casos con diagnóstico definitivo y probable de tuberculosis del sistema nervioso central; de acuerdo con los criterios de Marais, 38 % presentó coinfección por VIH/sida y 55 %, diversas comorbilidades (p = 0.0001); 49 % presentó alteraciones cognoscitivas y 14 % falleció. CONCLUSIONES: Aunque la infección por VIH/sida puede contribuir al deterioro cognitivo del paciente con tuberculosis meníngea, no se observaron diferencias entre pacientes con y sin VIH/sida. Las secuelas cognoscitivas mostraron mejoría en el seguimiento con el adecuado manejo y control terapéutico de los pacientes.

Intensified adjunctive corticosteroid therapy for CNS tuberculomas.

INTRODUCTION: Central nervous system (CNS) tuberculomas are a challenging manifestation of extrapulmonary tuberculosis often leading to neurological complications and post-treatment sequelae. The role of adjunctive corticosteroid treatment is not fully understood. Most guidelines on management of tuberculosis do not distinguish between tuberculous meningitis and CNS tuberculomas in terms of corticosteroid therapy. METHODS: We describe five patients with CNS tuberculomas who required intensified dexamethasone treatment for several months, in two cases up to 18 months. RESULTS: These patients were initially treated with the standard four-drug tuberculosis regimen and adjuvant dexamethasone. Neurological symptoms improved rapidly. However, multiple attempts to reduce or discontinue corticosteroids according to guideline recommendations led to clinical deterioration with generalized seizures or new CNS lesions. Thus, duration of adjunctive corticosteroid therapy was extended eventually leading to clinical cure and resolution of lesions. CONCLUSION: In contrast to tuberculous meningitis, the treatment for CNS tuberculomas appears to require a prolonged administration of corticosteroids. These findings need to be verified in controlled clinical studies.

Tuberculosis treatment in children: The changing landscape.

Traditionally children have been treated for tuberculosis (TB) based on data extrapolated from adults. However, we know that children present unique challenges that deserve special focus. New data on optimal drug selection and dosing are emerging with the inclusion of children in clinical trials and ongoing research on age-related pharmacokinetics and pharmacodynamics. We discuss the changing treatment landscape for drug-susceptible and drug-resistant paediatric tuberculosis in both the most common (intrathoracic) and most severe (central nervous system) forms of disease, and address the current knowledge gaps for improving patient outcomes.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Multi-spectral Pattern of Clinical Presentation and the Resultant Outcome in Central Nervous System Tuberculosis: A Single Center Study on the Ubiquitous Pathogen.

Central nervous system (CNS) tuberculosis (TB) is a great medical masquerader having a multi-spectral pattern of clinical presentation, thereby complicating early diagnosis and appropriate management. This review article describes clinical presentation of CNS TB in a group of 47 patients, who were managed in the Nobel Medical College and Teaching Hospital in Biratnagar, Nepal during the last 2 years. We evaluated demographic profile, mode of management, and clinical outcome in these patients. The findings were that intracranial TB was present in 27 (57.5%) patients and the spinal involvement was in 20 (42.5%) patients. The most frequent presentation of the former was TB meningitis with hydrocephalus (55.5%) and that of the latter was Pott's spine with abscess in 50% of cases. TB meningitis with hydrocephalus was the commonest cause of mortality (83.3%) among the patients. CNS TB should be considered in the differential diagnosis in patients presenting with equivocal neurological signs and symptoms, especially in TB endemic regions. It seems prudent to commence early antitubercular therapy for safeguarding such patients from poor neurological outcome as well as mortality it harbingers.

Central Nervous System involvement in tuberculosis: An MRI study considering differences between patients with and without Human Immunodeficiency Virus 1 infection.

BACKGROUND: Magnetic resonance imaging (MRI) is largely used in the diagnosis of central nervous system involvement of tuberculosis (CNSTB), yet there is no MRI comparison study between HIV+ and HIV- patients with CNSTB. The aim of the present study was to identify MRI differences in CNSTB between HIV+ and HIV- patients and possibly find early characteristics that could raise the suspect of this disease. METHODS: We included all patients admitted in our institution between 2011 and 2018 with confirmed diagnosis of CNSTB, and MRI performed in the first week. Patients with preexisting brain pathology or immunodeficiency not HIV related were excluded. We compared CNSTB MRI features between the two groups. RESULTS: Sixty-nine patients were included (19 HIV+; 50 HIV-). Findings in HIV+ group: 6 lung TB, 5 hydrocephalus, 4 meningeal enhancement, 6 stroke, 2 hemorrhages, and 10 tuberculomas. HIV- group: 22 lung tuberculosis, 15 hydrocephalus, 21 meningeal enhancement, 5 stroke, 4 hemorrhages, 20 tuberculomas. The only statistically significant difference between the two groups was in the stroke occurrence, more frequent in the HIV+ group (P=.028), all involving the basal ganglia. CONCLUSIONS: Stroke involving the basal ganglia best differentiates CNSTB patients who are HIV+ from those HIV-. This finding was not correlated with meningeal enhancement suggesting that small arteries involvement might precede it. Therefore, we think that HIV+ patients with a new onset of stroke should be evaluated for CNSTB. Follow-up MRI should also be planned since meningeal enhancement might appear in later stages of the disease.